A human gene will be studied in detail. The human genes for ribosomal DNA will be analyzed as members of a repetitious family of genes located on five non-homologous chromosome pairs. The ribosomal genes are members of an ancient evolutionary family whose primary transcript of 13 Kb is processed to mature 18, 28 and 5.8S RNA. This transcribed sequence is found within a very large 40 Kbp sequence which is tandemly repeated 20-30 times on the short arms of each of the five acrocentric chromosomes. Our work in progress has demonstrated that some sections of this 40 Kb repeat are rigidly conserved throughout the biological world. Other regions, such as that 3' to 28S sequence, are different in every species examined. The variable region not only shows variation between closely related species but between populations, individuals, within a set of chromosomes, and within a single chromosome. We will study the central questions of what factors contribute to human variation and what factors conserve gene structure. The changes which occur in a single gene are found in all of the genes on nonhomologous chromosomes. There is far greater similarity between genes on nonhomologous chromosomes than would be predicted by the diversity between genes on nonhomologous chromosomes than would be predicted by the diversity between closely related species. This concerted evolution indicates that there is recombination and conversion between the genes on nonhomologous chromosomes. We will examine the DNA structure which is involved in recombination and host factors which mediate or prevent variation. The genes will be studied by mapping, base sequencing and analyis of secondary structure. This study gives us the opportunity to view the evolution of a large family of genes over the entire evolutionary span. The genes will be compared to our sequences of other primates and with published sequences of lower organisms. The recombination of genes on nonhomologous chromosomes will be stressed as a cause of human birth defects.